18 Sep 08

Antibiotics should not be considered in cases of premature labour where the mother’s waters have not broken and there are no obvious signs of infection, a follow-up study on the children’s later health and development has confirmed.

The study, involving researchers at the National Perinatal Epidemiology Unit, Oxford University, is published in The Lancet.

The research consists of a seven-year follow up of a clinical trial, ORACLE, into the use of antibiotics in women presenting with signs of premature labour without obvious infection. It provides clinicians for the first time with evidence on the long-term effects on children of using antibiotics in women at risk of giving birth early.

The evidence obtained is crucial to ensuring women in these difficult circumstances receive the best clinical care for themselves and their babies. One in eight babies in the UK is born prematurely and prematurity is the leading cause of death in the first month after birth.

The original trial had found no benefit or harm on discharge from hospital of antibiotic administration in premature labour where the mother’s waters have not broken and there are no obvious signs of infection. The seven-year follow-up now shows there are increased risks of functional impairment and cerebral palsy in these children. The study, funded by the Medical Research Council, highlights the importance of conducting long-term follow-ups.

The ORACLE Trial was the largest trial worldwide into premature labour and was set up to investigate whether giving antibiotics – which might tackle an underlying symptomless infection – to women presenting with signs of premature labour would improve outcomes for babies. The trial recruited two groups of women: those whose waters had broken, and those who showed signs of going into premature labour whose waters had not broken.

The trial did not include pregnant women showing signs of infection as they should be treated with antibiotics. Untreated infections pose serious risks to both mother and baby.

Seven years ago, the ORACLE Trial reported that the administration of the antibiotic erythromycin to women whose waters had broken prematurely yielded short-term benefits. These included delaying the onset of labour as well as reducing the need for assistance with breathing and the rate of infection in babies. The follow-up study, designed to see whether better outcomes at birth made a difference to children’s later health and development, showed no benefit or harm in this group of children.

In women whose waters had not broken, the follow-up study shows that there is an increase in parents’ reporting of impairment in their children, most of which is ‘mild’  – from poor eyesight, to experiencing difficulty walking around the block or struggling with day-to-day problem-solving.

Parents also reported a small but statistically significant increase in the condition cerebral palsy (CP) in these children. CP is not a disease or an illness, it is the description of a physical impairment that affects movement. The movement problems vary from barely noticeable to extremely severe and no two people with CP are the same; it is as individual as people themselves.

‘Before the ORACLE Trial, there was some evidence of short-term benefits of antibiotics in premature labour, but we did not know what the long-term outcomes would be, which is why we conducted the follow-up,’ said Sara Kenyon from the University of Leicester who led the ORACLE Children Study. ‘It’s thanks to each and every one of the mothers who were involved in the original trial and the seven year follow-up study that we now have the evidence to inform clinical practice. We could not have obtained these results with a smaller group of participants. The size of the study means that we were able to pick up such small differences in these outcomes.’

Dr Kenyon added, ‘It is unclear why the follow-up showed this unexpected increase in the number of cases of cerebral palsy in babies born to the group of women whose waters had not broken and not in the other group.’

Dr Catherine Elliott, Head of Clinical Research Support and Ethics at the Medical Research Council (MRC), said: ‘The ORACLE Children Study highlights the importance of conducting long-term follow-ups, especially in interventions in pregnancy and early life. The results were unexpected and the MRC is considering what further research could shed more light on these findings. We will be convening an expert group to look at what potential research avenues could be explored to understand what mechanisms may be involved.’